Gastric Lymphoma Research Articles

MALT gastric lymphoma

MALT gastric lymphoma

FLI-1 is expressed in a wide variety of hematolymphoid neoplasms: a special concern in the differential diagnosis

Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing’s sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing’s sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.

Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation.

Introduction: Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy. Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis. Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.

Awardee Summary of 2023 Taiwan Oncology Society Clinical Research Award Recipient: Persistent Endeavors on Research of Digestive Cancers for Three Decades

Abstract Objective: Digestive cancers account for five of the top ten cancer-related deaths in Taiwan. Our team has made persistent endeavors in translational research and clinical trials of digestive cancers for almost three decades. Data Sources and Study Selection: We enrolled relevant translational and clinical studies for digestive cancers published by our groups in the past three decades. Results: First, we developed a unique weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin regimen (HDFL) in 1992. HDFL exhibits satisfactory single-agent activity, minimal myelosuppression, and mild toxicity. A variety of HDFL-based doublet combinations (such as cisplatin-HDFL, oxaliplatin-HDFL, and paclitaxel-HDFL) have become cornerstone regimens for three decades for the treatment of gastric cancers, with high efficacy and manageable toxicity at our hospital. Second, we have made persistent efforts in translational research and clinical trials on early-stage gastric mucosa-associated lymphoid tissue lymphomas (MALTomas), gastric diffuse large B-cell lymphomas, colorectal cancers (CRCs), pancreatic cancers, and immuno-oncology. Third, on behalf of the Taiwan Oncology Society, we participated in and published the Pan-Asian adapted European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for locally advanced and metastatic CRC, gastric, and esophageal cancers, and the consensus meeting on tumor-agnostic indications of microsatellite instability-high (MSI-H) and NTRK. Conclusion: In the future, our team will make persistent endeavors in research on digestive cancers for immunotherapy and precision medicine to further improve treatment outcomes.

An Overview of the Bench to Bedside Models of Breast Cancer in the Era of Cancer Immunotherapy

Lymphoma involves abnormal lymphoid cell growth, often originating in lymphatic tissue, but in this case series non-Hodking's lymphoma is visible in the extra-nodal region. This research explores different lymphoma cases, focusing on diverse presentations and utilizing modern imaging for evaluation. Four cases are detailed, involving an 18-year-old woman with tonsillar lymphoma, a 69-year-old man with ocular lymphoma, a 38-year-old lady with abdominal lymphoma, and a 30-year-old man with gastric lymphoma. All cases received adjuvant chemotherapy (RCHOP), leading to significant symptom relief after four cycles. One of the barriers to novel treatment developments within breast cancer is the ability to prove efficacy in the preclinical setting before moving on to clinical trials. Preclinical models range from single cell monolayers to more sophisticated humanised PDXs systems each with their set of advantages and limitations. Modelling the immune environment in cold tumours, such as breast cancer can also be challenging as are currently no clearly defined markers that can stratify patients based on treatment response. Immune checkpoints receptors such as PD-L1 may not show predictive outcomes in this tumour type. Furthermore, the heterogeneity of breast cancer may be difficult to recapitulate at the bench side. In this review, we provide an overview of the available in vitro, in vivo and ex vivo models of breast cancer with consideration of how these may extrapolated to the investigation of the role of the immune system and immunotherapy developments in breast cancer.

An uncommon presentation of gastric lymphoma in young male patient: mimicking acute necrotizing pancreatitis clinically and on blood investigations

An uncommon presentation of gastric lymphoma in young male patient: mimicking acute necrotizing pancreatitis clinically and on blood investigations

SARS-CoV-2-Related Persistent Pulmonary Affection Case in A 55-Year-Old Gastric MALT Lymphoma Patient on Rituximab

Following a mild symptomatic SARS-CoV-2 infection, a 55-year-old patient with gastric MALT lymphoma, currently treated with rituximab, experienced persistent symptoms. Over subsequent months, the patient exhibited low-grade fever, dyspnea, and progressive desaturation, leading to respiratory failure necessitating home oxygen therapy. A PCR test confirmed SARS-CoV-2 infection, prompting suspicion of persistent COVID-19. Imaging and biopsy results were consistent with cryptogenic organizing pneumonia (COP), but the patient showed no response to treatment, including corticosteroids and immunosuppressants. Remdesivir treatment yielded partial improvement but failed to achieve full resolution. Plitidepsin (2.5 mg/day for 3 days) under compassionate use led to negative PCR tests and normal respiratory function restoration within 3 days after treatment. SARS-CoV-2's impact on immunocompromised patients is concerning due to unique clinical features, challenges in viral clearance and immunization, and varied responses to approved treatments. A phase II clinical trial is underway to assess plitidepsin's efficacy in immunocompromised COVID-19 adults requiring hospital care.

Molecular profile of Epstein–Barr virus in representatives of four ethnic groups of Russia: virus types, <i>LMP1</i> gene variability and malignancies

Rationale. The discovery of two Epstein–Barr virus (EBV) types, EBV-1 and EBV-2, which differ in their transforming abilities stimulated their study in various populations in order to elucidate the relationship with malignant neoplasms.Aim. To study EBV-1 and EBV-2 in representatives of four ethnic groups of Russia, sequence analysis of the LMP1 oncogene in virus isolates, and search for a correlation between the types of EBV and the incidence of certain types of malignant tumors in four ethnic groups.Materials and methods. From total DNA obtained from oral washings of Adygeans, Kalmyks, Tatars and Slavs, representatives of 3 Russian republics and the Moscow region, EBV DNA was amplified; its presence and concentration were analyzed by nested PCR, and each product was examined for the virus type and LMP1 variant. Types of EBV found in representatives of In four ethnic groups were compared with the incidence rates of malignant tumors, among which EBV-associated cases may occur, in population of three republics and the Moscow region.Results. It was observed that higher gastric cancer and lymphomas morbidity among Tatarstan and Moscow region populations (compared to populations of Adygea and Kalmykia) correlated with predominance in these ethnic groups – Tatars and Slavs – EBV-1 type having transforming potential in vitro. In Adygeis, non-transforming EBV-2 type was prevalent, and Kalmyks were infected with both types in approximately equal proportion. however, differences between tumor morbidities between the compared groups were statistically insignificant (p >0.05). The identified spectrum of LMP1 variants, as well as the results of their sequencing, show genetic relations between EBV strains circulating in the studied ethnic groups.Conclusion. Study of EBV isolates for the first time performed in 4 ethnic groups of this country showed differences in distribution of the types of this virus but there was no correlation with tumor morbidity.

Endoscopic criteria for early differential diagnosis of gastritis-like form of primary non-Hodgkin's lymphomas and gastric cancer: A prospective study

Aim. To reveal and study basic endoscopic differential-significant criteria characterizing gastric-like form of primary non-Hodgkin's lymphoma (NHL) from adenocarcinoma and signet-ring cell carcinoma (SRCC) of the stomach.
 Materials and methods. In the prospective study, based of Blokhin National Medical Research Center of Oncology in the period from 2019 to June 2023, 106 patients with gastritic-like forms of primary NHL, adenocarcinoma and SRCC of the stomach were analyzed. Complex endoscopic study included examination in the modes of white light, magnification, narrow-band imaging (NBI, BLI, LCI) was done.
 Results. All patients were divided into three groups: MALT gastric lymphoma (38 patients, 35.8%), gastric adenocarcinoma (33 patients, 31.1%), and SRCC (35 patients, 33.1%). At MALT-lymphoma the tumor was localized in the antrum of the stomach (52.6%),adenocarcinoma and SRCC – in the body (45.5 and 60%). In the tumor structure in MALT-lymphoma of the stomach in 100% of cases multiple point areas of microdepressions and multicenter character of the lesion were determined. At adenocarcinoma – depressed area in the central part of tumor (45.5%), at SRCC – extended areas of microdepressions (51.4%) and multicentric character of lesions. At MALT-lymphoma the pit pattern in 63.2% is of "balloon" type, vascular – of tree-like type (84.2%). In adenocarcinoma the vascular pattern was of the loop-type (42.4%), in SRCC – of the corkscrew-type (74.3%). Demarcation line was observed only in adenocarcinoma (100%). At endosonographic study at MALT-lymphoma the tumor was coming from deep layers of mucous coat (100%), changes of regional lymph nodes (LN) were absent, at adenocarcinoma – from mucous membrane (100%), LN were not changed, at SRCC – submucous spread of tumor (100%), changes in LN (40%).
 Conclusion. Complex endoscopic examination is necessary to improve the quality of endoscopic examination of malignant gastric-like tumors, to determine the depth of invasion and spread of the tumor process, to assess the regional lymph drainage.

Amoxicillin-loaded Nanotechnological Carriers for the Effective Treatment of Helicobacter pylori Infection

Background: The bacterium Helicobacter pylori (H. pylori) is known to cause gastroduodenal disorders associated with the stomach lining that grows in the gastrointestinal tract, and can cause gastritis, peptic ulcer, gastric lymphoma, and stomach cancer. Nearly 50% of people worldwide suffer from H. pylori infection. This infection is more prominent in poor nations and undeveloped countries, and is caused by multiple factors, such as consumption of unhygienic food, crowded living style, etc. In the eradication treatment of gastric H. pylori infection, conventional dosage forms have various adverse effects on patients. Methods: In this study, we have explored current developments in the utilization of nanotechnological carriers for the successful management of H. pylori infection. In order to combat rising amoxicillin resistance, this review has focused on therapeutic strategies that use cyclodextrins, niosomes, liposomes, microspheres, nanoparticles, solid lipid nanoparticles, and nanostructure nanoparticles to improve therapy against H. pylori. Results: The entrapment of amoxicillin in various nanotechnological carriers enhances its effectiveness and reduces adverse effects. These carriers lead to targeted drug release and improve drug penetration to the gastroduodenal disease site that locally controls and adjusts the drug release. Conclusion: For the effective treatment of H. pylori infection, nanotechnological carriers have provided a new avenue for the development of innovative, high-impact, and low-dose systems. The main objective of this review was to outline the present limitations of H. pylori therapy and new potential alternatives, as well as to report how nanotechnological carriers may be used to overcome treatment shortcomings.

Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients

Background/Objectives: Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy. Materials/Methods: 285 consecutive pts with PG lymphomas treated with RT between 1/2000-1/2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE v4.0. Results: Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 years (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-year OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT. Conclusion: Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.

Ultra Low Dose 4 Gy Radiation for Definitive Therapy of Gastric MALT Lymphoma

Introduction Definitive treatment for early-stage gastric MALT (mucosa-associated lymphoid tissue) lymphoma typically includes radiation therapy (RT) to doses of 24-30 Gy. Given the favorable prognosis of this disease, there is considerable interest in decreasing the toxicity profile of treatment. We prospectively investigated outcomes using a response-adapted (RA) approach giving an initial 4 Gy (ultra-low dose (ULD)) RT with an additional 20 Gy only for incomplete response (Figure 1). We hypothesized that this RA-approach would maintain excellent outcomes with limited toxicity. Methods We performed a single-arm prospective trial of ULD RT in 24 patients (age ≥18 years) with newly diagnosed or relapsed stage I-IV H. pylori (HP) negative gastric MALT lymphoma (NCT03680586). Patients with residual lymphoma after HP eradication were eligible. Patients with bulky disease (>10 cm) were excluded. Patients were treated with 4 Gy in 2 fractions and assessed with endoscopy and imaging at 3-4 months post-RT. Patients with a complete response (CR) assessed by endoscopy with biopsies and imaging were observed. Patients with a partial response (PR) by endoscopic, pathologic or radiographic evaluations were re-evaluated in 6-9 months. Biopsy-confirmed residual disease at the second timepoint (9-13 months) or stable disease (SD)/progressive disease (PD) at any time point prompted treatment with an additional 20 Gy in 10 fractions. Systemic therapy was permitted if clinically indicated. Results We enrolled 24 patients from 2019-2021. Median age was 67 (range 40-85) with 15 female patients (63%). Patients had stage I (n=20, 83%), II (n=1, 4%), and IV (n=3, 13%) disease. Of 15 tested patients, 4 were positive for t(11;18). Patients had pre-treatment imaging with fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) (n=21), contrasted CT (n=2), and contrasted magnetic resonance imaging (MRI) (n=1). Eight patients had prior treatment including systemic therapy (n=2, 8%) or antibiotics for HP positive (n=3, 13%) or HP negative (n=3, 13%) disease. Of 3 patients with prior HP positive disease, residual lymphoma was documented after eradication at 18 months (PR), 11 months (SD), and 8 months (disease relapse after CR) post-diagnosis. Median follow-up for the entire cohort was 34 months (95% CI 22-40) based on the reverse Kaplan-Meier estimator. Sixteen patients had a CR at first evaluation (3-4 months) after 4 Gy, and an additional 4 patients had disease conversion to CR at second evaluation (9-13 months), for a total of 20 patients (83%) who had a CR to 4 Gy at a median time of 4 months (range 3-12). No patients had positive imaging findings with a pathologic CR. One local relapse occurred 14 months post-treatment after a CR to 4 Gy. This patient received 20 Gy and again experienced a CR. Four patients received an additional 20 Gy for SD/PD or residual disease after 4 Gy. Two patients received 20 Gy for symptomatic SD at 3-4 months, both with a CR following RA therapy. Two patients received 20 Gy for residual disease at 10 and 13 months. One patient had a CR and one is pending last follow-up. Two of the 4 patients (50%) with a positive t(11;18) required an additional 20 Gy RT compared with 3 of 11 (27%) patients without the translocation (p=0.56) The rate of 3-year LC for 23 patients who had complete follow-up was 100%, with 19 of 24 patients (79%) with a CR at last follow-up after only the initial 4 Gy. One patient with stage IV disease experienced distant relapse with diffuse large B cell lymphoma and is in CR after systemic therapy. No additional patients received systemic therapy after RT. RT was well tolerated with no grade 3 or higher acute or late toxicities. Conclusions Most patients with gastric MALT lymphoma experienced a CR after only 4 Gy RT; for those requiring an additional 20 Gy with completed follow-up, all experienced a CR. This strategy could be considered to select only those patients who benefit from longer RT courses and spare most patients from unnecessary treatment toxicity. It is important to allow adequate time for response with this indolent disease. Additional follow-up is required to confirm long-term excellent outcomes with RA ULD treatment.

Clinicopathologic Features and Survival Outcomes of Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma) of the Urothelial Organs (Urologic MALT Lymphoma): The Mayo Clinic Experience (2013-2022)

Introduction: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell non-Hodgkin lymphoma that originates in lymphoid tissue of epithelial lined structures. The commonest site for this lymphoma is the stomach (gastric MALT lymphoma). MALT lymphoma in other mucosal sites, including other gastrointestinal sites, lungs, salivary glands, and lacrimal glands, has been well-described. However, MALT lymphoma in urothelial organs (kidneys, ureters, and urinary bladder) has not been well-characterized. This study aimed to investigate the clinicopathological features and therapeutic outcomes in urologic MALT lymphoma (U-MALT). Methods: We identified patients with U-MALT who were treated at the Mayo Clinic Cancer Center between March 2013 and May 2022 through electronic medical chart review. Clinical, pathologic, radiologic, therapeutic, and survival data were extracted. Kaplan-Meier analysis was used to determine the survival outcomes. Results: The characteristic features of six patients (N=6) with U-MALT are summarized in Table-1. 4/6 (67%) are Caucasian, and 3/6 (50%) are males. The median age at diagnosis was 73.5 years. Urologic sites are the urinary bladder (3/6), kidneys (3/6), and ureter (1/6, this patient had both kidney and ureter involvement). 4/6 patients had primary U-MALT. Concurrent non-urologic involvement was identified in 3/6 patients and included bone marrow, lungs, stomach, and axillary lymph nodes. Bone marrow involvement was observed in 2/6 patients.Next-generation sequencing was performed on one patient's peripheral blood, revealing an ATM mutation. Regarding the initial clinical presentation, kidney-involved U-MALT patients presented with renal failure, and those with urinary bladder/ureteric involvement, U-MALT was diagnosed incidentally upon cystoscopic evaluation and biopsy. Various management strategies were used, including observation, surgical resection, and rituximab treatment. Notably, all patients achieved complete remission (CR) except one with partial response to rituximab, who subsequently achieved CR with the Bendamustine/Rituximab regimen. Median follow-up is 6 years (range, 1-10). All six patients are alive without relapse at the time of analysis, with the flat overall survival curve at 100%, indicating excellent long-term survival. Conclusions: Our study indicates that urologic MALT lymphomas are extremely rare and predominantly affect elderly people. The most common urologic sites are the kidneys and urinary bladder. Urologic manifestations are dependent on the urologic site involved. They can be primary to the urologic structures or part of the disseminated systemic marginal zone lymphoma. They can be treated like other low-grade lymphomas with observation, surgical resection, and systemic therapy. They appear to be quite responsive to CD-20 targeted therapy with Rituximab. Prognosis appears to be excellent with long overall survival. Further research with multi-institutional studies is needed to study this rare lymphoma entity and identify optimal therapy.

Endoscopic features of helicobacter pylori-uninfected gastric malt lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma that develops in extranodal organs (e.g., gastrointestinal tract, thyroid gland, and lungs) against the background of chronic inflammation. Approximately 80%-90% of gastric MALT lymphomas

Gastric microbiota in patients with gastric MALT lymphoma according to Helicobacter pylori infection

Gastric Mucosa Associated Lymphoid Tissue lymphoma (GML) development is triggered by Helicobacter pylori (H. pylori) infection. Little is known about the impact of H. pylori infection on gastric microbiota. The gastric microbiota was retrospectively investigated using 16S rRNA gene sequencing in 32 patients with untreated GML (10 H. pylori-positive and 22 H. pylori-negative), 23 with remitted and 18 refractory GML and 35 controls. Differences in microbial diversity, bacterial composition and taxonomic repartition were assessed. There was no change in diversity and bacterial composition between GML and control patients taking into account H. pylori status. Differential taxa analysis identified specific changes associated with H. pylori-negative GML: the abundances of Actinobacillus, Lactobacillus and Chryseobacterium were increased while the abundances of Veillonella, Atopobium, Leptotrichia, Catonella, Filifactor and Escherichia_Shigella were increased in control patients. In patients with remitted GML, the genera Haemophilus and Moraxella were significantly more abundant than in refractory patients, while Atopobium and Actinomyces were significantly more abundant in refractory patients. Detailed analysis of the gastric microbiota revealed significant changes in the bacterial composition of the gastric mucosa in patients with GML that may have a role in gastric lymphomagenesis but not any new pathobionts.

Advances in Helicobacter pylori vaccine research: From candidate antigens to adjuvants-A review.

Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric-related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection. PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms-H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed. Most of the candidate antigens used as H. pylori vaccines in these literatures are whole-cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible. This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers.

Effects of Antibiotic Eradication Therapy on H. Pylori-Negative Stage IE Gastric MALT Lymphoma ─ Real World Experience

Background: Helicobacter pylori (H. pylori) infection plays a critical role in the pathogenesis of gastric MALT lymphoma and its eradication can lead to tumor regression with a complete response (CR) rate of 78% in early-stage disease and a 5-year survival rate > 95%. However, 10% of patients have gastric MALT lymphoma with no detectable H. pylori infection (Zullo et al., J Clin Gastroenterol 2010). There is controversy regarding whether H. pylori-negative gastric MALT patients should receive a trial of antibiotic therapy. The NCCN guideline recommends skipping antibiotics and proceeding directly to radiation therapy. On the other hand, the ESMO guideline recommends H. pylori eradication (HPE) as the first-line therapy for every patient with gastric MALT lymphoma irrespective of H. pylori status. This report aimed to evaluate the effectiveness of H. pylori eradication therapy in patients with limited-stage gastric MALT lymphoma. Methods: A retrospective analysis was performed to identify patients diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. H. pylori infection was determined by immunostaining of gastric mucosa, serology, stool antigen, or urea breath test. H. pylori status was considered positive when at least one of those tests showed positive results and negative when all of the performed test results in that patient were negative. The primary outcome was the CR rate defined as no macroscopic findings of lymphoma and negative biopsy resultsfrom the follow-up endoscopy 3-6 months following completion of treatment. Results: A total of 52 patients were identified; the median age was 68 years (range 52-87), and 29 (55.8%) were male. H. pylori infection was detected in 36.5% (19/52) patients by at least one of the methods - 14 cases by immunostaining, 3 cases by serology, and 1 each by stool antigen and urea breath test. The PCR or FISH for t(11;18) was performed in 10 cases (19.2%) and 2 cases of t(11;18) were detected (both were H. pylori-negative). All 19 H. pylori-positive patients were treated for H. pylori eradication (HPE) and 63% (12/19) achieved a CR. Of the 33 H. pylori-negative patients, 8 (24.2%) received HPE as the initial treatment and 1 (12.5%) responded with a CR. The treatment outcomes after HPE therapy showed the CR rate was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (63.2% vs 12.5%, p=0.033) (Table 1). Only 2 of the 12 H. pylori-positive patients achieving CR have relapsed after a median follow-up of 89.7 months (range 2.9-227.8); the one H. pylori-negative patient that received HPE also remains in CR at 9+ months. The other first-line treatments applied for the 25 H. pylori-negative patients were radiation therapy in 18 (54.5%), single-agent rituximab in 3 (9.0%), surgical resections in 2 (6%), oral chlorambucil in 1 (3%), and observation in 1 (3%) The outcomes are shown in Figure 1. Conclusion: In our United States patient population, the incidence of H. pylori-negative gastric MALT lymphoma was 63%, much higher than previously reported (Zullo et al., J Clin Gastroenterol 2010) and similar to that found by other US investigators (Strati et al. 10.1002/ajh.25447). For limited-stage H. pylori-positive gastric MALT lymphoma, HPE is an effective first-line treatment and should be used. For patients who have no detectable H. pylori infection with multiple methods, the CR rate with HPE is very low in our experience. Although there is likely little harm to trying HPE (as ESMO guidelines suggest), this delays definitive radiation therapy. These data will be useful in patient counseling and treatment decision-making.

Metachronous Testicular Mixed Germ Cell Tumour and Gastric Marginal Zone Lymphoma: A Case Report with An Unusual Association

Metachronous Testicular Mixed Germ Cell Tumour and Gastric Marginal Zone Lymphoma: A Case Report with An Unusual Association

A study of prevalence and risk factors for Helicobacter pylori infection among adults in Duhok Province, Kurdistan Region, Iraq.

Helicobacter pylori is known to increase the risk of developing gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma in adults across the globe. The present study aimed to determine the prevalence of H. pylori infection and its associated risk factors. This cross-sectional study was conducted among the adult population in Duhok Province, Kurdistan Region, Iraq. A total of 259 subjects over the age of 18 who visited the hospitals were included in the study from 2018 to 2020. An enzyme-linked immunosorbent assay was utilized to determine H. pylori seropositivity. A standardized questionnaire was administered to all study participants through face-to-face interviews. The H. pylori immunoglobulin G (IgG) antibody data were analyzed using the Chi-square test. The prevalence of anti-H. pylori IgG antibody was present in 40.02% of adults. Among the studied variables, the following risk factors were significantly associated with the presence of anti-H. pylori IgG antibodies: male gender (P<0.043), level of education (P<0.025), history of gastrointestinal diseases (P<0.001), smoking status (P<0.001), and more siblings (P<0.001). This study supports the hypothesis that H. pylori infection in adults is highly related to poor hygiene and smoking status, low level of education, and crowded conditions. Therefore, in order to reduce the prevalence of H. pylori infection among adults, it is crucial to implement effective strategies aimed at enhancing fundamental sanitary conditions, as well as improving educational and socioeconomic status.

The presence of H. pylori in laparoscopic sleeve gastrectomy specimens is associated with increased mucosal thickness, presence of secondary follicles, increased chronic inflammation, and intestinal metaplasia

ABSTRACT Helicobacter pylori is putatively present in over half of the global human population and is recognized as a carcinogenic agent that increases the likelihood of infected patients developing gastric adenocarcinoma or gastric lymphoma. Although there are several means for testing for H. pylori, the gold standard remains the invasive histologic evaluation. The current most popular form of bariatric surgery is the laparoscopic sleeve gastrectomy (LSG) and is the only bariatric surgery which supplies a specimen for histologic evaluation. While non-invasive testing is effective in diagnosing and monitoring H. pylori infection, histological examination of biopsies and resections is the only way to grade chronic inflammation and evaluate specimens for additional pathologies such as intestinal metaplasia. The investigators evaluated 203 sequential LSG specimens collected from a major metropolitan hospital over the period of one year. Specimens were processed to paraffin, stained with hematoxylin and eosin, alcian blue, and immunohistochemistry to determine the presence of H. pylori, chronic inflammation, presence of secondary lymphoid follicles in the mucosa, mucosal thickness, and presence of intestinal metaplasia. Statistical analyses demonstrated a significant positive correlation among all factors examined. The overall positivity rate of H. pylori in LSG specimens was 18.2% but ranged from 6.9−23.8% depending on whether the treating clinician performed routine pre-surgical endoscopy. The presence of H. pylori was associated with a higher average chronic inflammation grade, intestinal metaplasia, thicker mucosa, and presence of lymphoid follicles with germinal centers in the mucosa.